The broad objective of this research program is to gain understanding of the nature of diabetes mellitus in humans, particularly with regard to etiology and to mechanisms of pathological, physiological, and biochemical changes. The proposed approach to the pathobiology of diabetes mellitus focuses on four major interrelated areas: 1. insulin secretion; 2. insulin action; 3. the pathogenesis of different forms of diabetes; and 4. the pathogenesis of atherosclerosis in diabetes. Projects are proposed to study the role of prostaglandins in pancreatic islet function, regulation of prostaglandin-E receptors in pancreatic islets and adipocytes, studies of oscillatory secretion of somatostatin, mechanism of action of insulin on cell membranes, regulation of the function of lysosomes in diabetes, factors influencing the pathogenesis of insulin-dependent diabetes, obesity and adipose tissue lipoprotein lipase activity, particularly in relation to non-insulin dependent diabetes, the interactions of human arterial cells with lipoproteins, and the regulation of arterial cell metabolism in diabetes, and a common project involving several investigators focused on lipoprotein abnormalities in diabetes.